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Modulation of glutamate receptor trafficking in autism: role of MHC class I

City:

Princeton

State/Province:

NJ

State/Province Full:

New Jersey

Country:

United States

There is growing evidence of an imbalance in neuronal signaling in the brains of some individuals with autism. The neurotransmitter glutamate is an important chemical that “turns on” neurons. Direct measures of glutamate neurotransmission have been used to measure proper neuronal signaling in animal models. Recent studies have linked the ability of neurons to respond to the neurochemical glutamate to the changes in immune response. Because maternal immune challenge during pregnancy may be a risk factor for autism in children, this raises the possibility that maternal immune challenge may alter glutamatergic neurotransmission. This is may be accomplished through modification of MHC class I molecules (major histocompatibility complex class I) in the developing fetal brain. MHC-I molecules are an essential part of the immune response which are now known to be expressed in the brain and modulate neuronal function. Using a mouse model, Drs. Boulanger and Fourgeaud will test whether changes in MHC class I in the developing brain effects glutamate receptors, and whether these changes can be induced in the fetal brain by maternal immune challenge. Together with the projects mentored by Dr. McAllister and Dr. Patterson, the role of alterations in immune function on brain development and later behavioral function will be better understood. What it means for people with autism: These studies could also provide a mechanistic link between maternal immune challenge, a significant environmental risk factor for autism, and glutamatergic dysfunction, a hallmark symptom of this disorder. Furthermore, the results of these studies may suggest new, immune-based strategies for the diagnosis, treatment, and prevention of autism.